中国人群白介素1受体相关激酶4基因多态性与脓毒症易感性的相关性研究  

Genetic Association of IRAK4 Gene Polymorphisms with Risk of Sepsis in Han Chinese Population

作　　者：方宇[1] 张璐[2] 周钢桥[3] 曾昭书[4] 王志富[3] 罗志毅[1] 李垒[5] 刘保池[5] 

机构地区：[1]郑州大学第一附属医院急诊科,河南省高等学校临床医学重点学科开放实验室,郑州450052 [2]郑州大学第一附属医院神经内科,郑州450052 [3]军事医学科学院放射与辐射医学研究所,北京蛋白质组研究中心国家重点实验室,北京100850 [4]郑州大学基础医学院法医学教研室,郑州450001 [5]复旦大学附属公共卫生临床中心,上海201508

出　　处：《华中科技大学学报（医学版）》2011年第4期385-391,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家重点基础研究发展规划(973计划)(No·2005CB522602);北京市科技新星计划(No·2006A54);国家自然科学基金(No·31071100)资助项目

摘　　要：目的探讨白介素1受体相关激酶4(interleukin-1 receptor-associated kinase 4,IRAK4)多态性位点与脓毒症发生风险及疾病严重程度的关联性。方法采用Hapmap单倍型标签SNPs(htSNPs)策略和SNPstream分型方法,对255例脓毒症患者和260例对照个体进行分型。采用Logistic回归分析,校正性别、年龄、吸烟和饮酒、慢性病状态、A-PACHEⅡ评分和脓毒症病因等混杂因素的影响,评价IRAK4多态性位点与脓毒症的发生风险,以及脓毒症性休克、死亡和多器官功能障碍的遗传相关性。结果 IRAK4基因在中国人群中共捕获6个htSNPs。rs4251431 G/T,rs4251460A/C,rs4251513 G/C和rs4251545 G/A最终用于分型研究。4个htSNPs位点在病例和对照组中的基因型分布均呈Hardy-Weinberg平衡状态。IRAK4多态性位点及单倍体与脓毒症的发生风险和疾病严重程度均无明显相关性。结论在中国人群中,IRAK4基因多态性位点在脓毒症的发生、发展和病程转归中可能不发挥重要作用。Objective To explore the association between interleukin-1（IL-1）receptor-associated kinase 4（IRAK4）polymorphisms and the susceptibility to sepsis.Methods Haplotype tagging single nucleotide polymorphisms（htSNPs）were selected from the HapMap database.The htSNPs were genotyped in 255 patients with sepsis and 260 controls by the Beckman SNPstream genotyping platform.The association with susceptibility to and severity of sepsis was estimated by logistic regression with adjustment for age,sex,smoking,drinking,chronic diseases status,APACHEⅡ score and primary diseases status.Results Of 16 IRAK4 SNPs,6 were tagged by htSNPs.Of them,4 htSNPs（rs4251431 G/T,rs4251460 A/C,rs4251513 G/C and rs4251545 G/A）were used for final genotyping analysis.Genotype frequencies of those htSNPs were conformed to the Hardy-Weinberg law in both patients and controls.There were no significant associations found between the 4 htSNPs and susceptibility to sepsis after correction for multiple comparisons.Also,there was no significant association between the IRAK4 polymorphisms and the septic shock,death from sepsis as well as organ dysfunction.Conclusion The IRAK4 gene polymorphisms might not play a major role in severity of sepsis in the Han Chinese population.

关 键 词：白介素1受体相关激酶4 脓毒症 单倍型标签单核苷酸多态性 连锁不平衡 遗传关联 

分 类 号：R394[医药卫生—医学遗传学]